Diagnostic performance of metagenomic next-generation sequencing for the detection of pathogens in cerebrospinal fluid in pediatric patients with central nervous system infection: a systematic review and meta-analysis.

BACKGROUND: Detecting pathogens in pediatric central nervous system infection (CNSI) is still a major challenge in medicine. In addition to conventional diagnostic patterns, metagenomic next-generation sequencing (mNGS) shows great potential in pathogen detection. Therefore, we systematically evaluated the diagnostic performance of mNGS in cerebrospinal fluid (CSF) in pediatric patients with CNSI. METHODS: Related literature was searched in the Web of Science, PubMed, Embase, and Cochrane Library. We screened the literature and extracted the data according to the selection criteria. The quality of included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the certainty of the evidence was measured by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) score system. Then, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odd's ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) were estimated in Stata Software and MetaDisc. Subgroup analyses were performed to investigate the potential factors that influence the diagnostic performance. RESULTS: A total of 10 studies were included in the meta-analysis. The combined sensitivity was 0.68 (95% confidence interval [CI]: 0.59 to 0.76, I2 = 66.77%, p < 0.001), and the combined specificity was 0.89 (95% CI: 0.80 to 0.95, I2 = 83.37%, p < 0.001). The AUC of sROC was 0.85 (95% CI, 0.81 to 0.87). The quality level of evidence elevated by the GRADE score system was low. CONCLUSIONS: Current evidence shows that mNGS presents a good diagnostic performance in pediatric CNSI. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.

Recent pharmacological advances in the treatment of cardiovascular events with Astragaloside IV.

Cardiovascular disease (CVD) remains the leading cause of death and disability globally. A wide range of CVDs have been reported, each of which diverges significantly, exhibiting sophisticated types of pathogenesis (e.g., inflammatory, oxidative stress, and disorders in cardiomyocyte metabolism). Compared with conventional treatments in modern medicine, traditional Chinese medicine (TCM) can exhibit comparative advantages in the treatment of CVDs. TCM can be utilized to develop effective strategies for addressing the challenges of CVD, with fewer side effects and higher therapeutic efficiency. Astragaloside IV (AS-IV) has been confirmed as one of the major active ingredients found in Astragalus membranaceus (a Chinese herbal medicine that has been extensively employed clinically for the treatments of CVDs). Since recent studies have shown that AS-IV in CVD treatments has achieved promising results, the substance has aroused great attention and further discussions in the field. The present review aims to summarize the recent pharmacological advances in employing AS-IV in the treatment of CVDs.

Venous blood parameters in determination of respiratory impairment in amyotrophic lateral sclerosis.

This study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and develop a model to predict respiratory impairment for individual patients with ALS. A total of 416 ALS patients were included in the study, and various hematologic and biochemical laboratory parameters as well as demographic and clinical factors were collected and compared. A multivariable logistic regression model was constructed to assess the association between FVC and venous blood biomarkers and clinical factors. The results showed that along with onset age, bulbar-onset, disease duration, BMI, eosinophil count (EO#), basophil count (BASO#), creatinine (CREA), uric acid (URCI) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL/HDL) ratio were associated with reduced FVC. The area under the ROC curve is 0.735 for the test set and 0.721 for the validation set. The study also developed a relatively acceptable model for predicting respiratory impairment in ALS patients. These findings suggest that EO#, BASO#, CREA, URIC and LDL/HDL ratio can be useful in assessing FVC in ALS and can be easily accessible, accurate, and low-cost parameters.

The application of metagenomic next-generation sequencing in pathogen diagnosis: a bibliometric analysis based on Web of Science.

Background: Infectious disease is a large burden on public health globally. Metagenomic next-generation sequencing (mNGS) has become popular as a new tool for pathogen diagnosis with numerous advantages compared to conventional methods. Recently, research on mNGS increases yearly. However, no bibliometric analysis has systematically presented the full spectrum of this research field. Therefore, we reviewed all the publications associated with this topic and performed this study to analyze the comprehensive status and future hotspots of mNGS for infectious disease diagnosis. Methods: The literature was searched in the Web of Science Core Collection and screened without year or language restrictions, and the characteristics of the studies were also identified. The outcomes included publication years, study types, journals, countries, authorship, institutions, frontiers, and hotspots with trends. Statistical analysis and visualization were conducted using VOSviewer (version 1.6.16) and CiteSpace (version 6.1. R3). Results: In total, 325 studies were included in the analysis after screening. Studies were published between 2009 and 2022 with a significantly increasing number from 1 to 118. Most of the studies were original articles and case reports. Frontiers in Cellular and Infection Microbiology and Clinical Infectious Disease were the most commonly cited and co-cited journals. Institutions and researchers from China contributed the most to this field, followed by those from the USA. The hotspots and frontiers of these studies are pneumonia, tuberculosis, and central nervous system infections. Conclusion: This study determined that mNGS is a hot topic in the diagnosis of infectious diseases with development trends and provides insights into researchers, institutions, hotspots and frontiers in mNGS, which can offer references to related researchers and future research.

Circulating tumor DNA as liquid biopsy in lung cancer: Biological characteristics and clinical integration.

Lung cancer maintains high morbidity and mortality rate globally despite significant advancements in diagnosis and treatment in the era of precision medicine. Pathological analysis of tumor tissue, the current gold standard for lung cancer diagnosis, is intrusive and intrinsically confined to evaluating the limited amount of tissues that could be physically extracted. However, tissue biopsy has several limitations, including the invasiveness of the procedure and difficulty in obtaining samples for patients at advanced stages., there Additionally,has been no major breakthrough in tumor biomarkers with high specificity and sensitivity, particularly for early-stage lung cancer. Liquid biopsy has been considered a feasible auxiliary tool for tearly dianosis, evaluating treatment responses and monitoring prognosis of lung cancer. Circulating tumor DNA (ctDNA), an ideal biomarker of liquid biopsy, has emerged as one of the most reliable tools for monitoring tumor processes at molecular levels. Herein, this review focuses on tumor heterogeneity to elucidate the superiority of liquid biopsy and retrospectively discussdeciphersolution. We systematically elaborate ctDNA biological characteristics, introduce methods for ctDNA detection, and discuss the current role of plasma ctDNA in lung cancer management. Finally, we summarize the drawbacks of ctDNA analysis and highlight its potential clinical application in lung cancer.

Single-cell transcriptome analysis reveals cellular and molecular alterations in small cell lung cancer tumors following chemotherapy.

Chemotherapy is the standard therapy for small cell lung cancer (SCLC), but relapse is common and the 2-year survival rate remains low. Given the contribution of the tumor microenvironment (TME) to cancer development and response to treatment, we analyzed here how chemotherapy alters the TME in SCLC using single-cell RNA sequencing. The comparison between neuroendocrine cells and other epithelial cells in five chemotherapy-naive patients identified upregulation of Notch-inhibiting genes, such as DLL3 and HES6. Analysis of genes differentially expressed between five patients receiving chemotherapy and five treatment-naive patients in cells in the TME showed that chemotherapy promoted antigen presentation and senescence in neuroendocrine cells, upregulated ID1 to enhance angiogenic activities of stalk-like endothelial cells and strengthened vascular endothelial growth factor signaling in lymphatic endothelial cells. Chemotherapy also promoted the remodeling of extracellular matrix by fibroblasts and upregulated interferon-mediated antitumor immune responses by B and T cells. Our single-cell transcriptome analysis provides insights into how chemotherapy affects the TME in SCLC, which may guide efforts to make therapy more effective.

Epigenetic regulation of stem cells in lung cancer oncogenesis and therapy resistance.

Epigenetics plays an important role in regulating stem cell signaling, as well as in the oncogenesis of lung cancer and therapeutic resistance. Determining how to employ these regulatory mechanisms to treat cancer is an intriguing medical challenge. Lung cancer is caused by signals that cause aberrant differentiation of stem cells or progenitor cells. The different pathological subtypes of lung cancer are determined by the cells of origin. Additionally, emerging studies have demonstrated that the occurrence of cancer treatment resistance is connected to the hijacking of normal stem cell capability by lung cancer stem cells, especially in the processes of drug transport, DNA damage repair, and niche protection. In this review, we summarize the principles of the epigenetic regulation of stem cell signaling in relation to the emergence of lung cancer and resistance to therapy. Furthermore, several investigations have shown that the tumor immune microenvironment in lung cancer affects these regulatory pathways. And ongoing experiments on epigenetics-related therapeutic strategies provide new insight for the treatment of lung cancer in the future.

Crisis communication in the WHO COVID-19 press conferences: A retrospective analysis.

OBJECTIVES: The objective of this study is to investigate, from a longitudinal perspective, how WHO communicated COVID-19 related information to the public through its press conferences during the first two years of the pandemic. METHODS: The transcripts of 195 WHO COVID-19 press conferences held between January 22, 2020 and February 23, 2022 were collected. All transcripts were syntactically parsed to extract highly frequent noun chunks that were potential topics of the press conferences. First-order autoregression models were fit to identify "hot" and "cold" topics. In addition, sentiments and emotions expressed in the transcripts were analyzed using lexicon-based sentiment/emotion analyses. Mann-Kendall tests were performed to capture the possible trends of sentiments and emotions over time. RESULTS: First, eleven "hot" topics were identified. These topics were pertinent to anti-pandemic measures, disease surveillance and development, and vaccine-related issues. Second, no significant trend was captured in sentiments. Last, significant downward trends were found in anticipation, surprise, anger, disgust, and fear. However, no significant trends were found in joy, trust, and sadness. CONCLUSIONS: This retrospective study provided new empirical evidence on how WHO communicated issues pertaining to COVID-19 to the general public through its press conferences. With the help of the study, members of the general public, health organizations, and other stake-holders will be able to better understand the way in which WHO has responded to various critical events during the first two years of the pandemic.

Graphite Nanoflake-Modified Mo2C with Ameliorated Interfacial Interaction as an Electrocatalyst for Hydrogen Evolution Reaction.

Molybdenum carbide (Mo2C) is anticipated to be a promising electrocatalyst for electrocatalytic hydrogen production due to its low cost, resourceful property, prominent stability, and Pt-like electrocatalytic activity. The rational design of Mo2C-based electrocatalysts is expected to improve hydrogen evolution reaction (HER) performance, especially by constructing ultrasmall Mo2C particles and appropriate interfaces. Herein, composites of molybdenum carbide (Mo2C) quantum dots anchored on graphite nanoflakes (Mo2C/G) were fabricated, which realized a stable overpotential of 136 mV at 10 mA cm-2 for the HER with a small Tafel slope of 76.81 mV dec-1 in alkaline media, and operated stably over 10 h and 2000 cycles. The superior HER performance can be attributed to the fact that graphite nanoflakes could act as a matrix to disperse Mo2C as quantum dots to expose more active sites and guarantee high electronic conductivity and, more importantly, provide ameliorated interfacial interaction between Mo2C and graphite nanoflakes with appropriate hydrogen binding energy and charge density distribution. To further explore which kind of interfacial interaction is more favorable to improve the HER performance, density functional theory calculations and corresponding contrast experiments were also performed, and it was interesting to prove that Mo2C quantum dots anchored to the basal planes of defective graphite nanoflakes exhibit better electrochemical performance than those anchored on the edges.

SARS-CoV-2-inactivated vaccine hesitancy and the safety in inflammatory bowel disease patients: a single-center study.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine is thought to be the most effective preventive method of controlling the coronavirus disease 2019 (COVID-19) epidemic. Some patients with immune-related diseases, including inflammatory bowel disease (IBD) patients, however, may hesitate to be vaccinated for various reasons. Although several guidelines recommend vaccinating all IBD patients with inactivated SARS-CoV-2 vaccines, there is still a lack of real-world data on the safety of inactivated SARS-CoV-2 vaccines and COVID-19 vaccination rate in IBD patients. In this study, we investigated the reasons for hesitancy in COVID-19 vaccination, the COVID-19 vaccination rate, and the safety of SARS-CoV-2-inactivated vaccination in patients with IBD. Methods: This was a retrospective study. A total of 418 participants with IBD were enrolled to calculate the vaccination rates. A total of 232 patients with IBD who did not receive SARS-CoV-2 vaccination were recruited to investigate the reasons for hesitation. A follow-up survey of 151 IBD patients and 188 healthy participants who had received the SARS-CoV-2-inactivated vaccination was conducted to analyze adverse reactions. Results: The COVID-19 vaccination rate was 49.3% and almost half of the participants were 'Concerned about the safety of the vaccine (such as adverse reactions) due to IBD'. After SARS-CoV-2 vaccination, adverse reactions were mild or moderate. The adverse reactions in the IBD and non-IBD populations were roughly the same, and IBD medications did not increase the risk of adverse reactions. Conclusion: SARS-CoV-2-inactivated vaccination rates in IBD patients are still low and a significant proportion of patients are hesitant about the vaccine because of safety concerns. SARS-CoV-2-inactivated vaccination in patients with IBD appears to be safe.

A Prediction Model for Peak Expiratory Flow Derived From Venous Blood Biomarkers and Clinical Factors in Amyotrophic Lateral Sclerosis.

Although peripheral venous blood biomarkers are related to respiratory function in Amyotrophic lateral sclerosis (ALS) patients, there are still few prediction models that predict pulmonary function. This study aimed to investigate the venous blood biomarkers associated with respiratory function in patients with ALS from southwest China and to create prediction models based on those clinical biomarkers using logistic regression. A total of 319 patients with ALS from the retrospective cohort and 97 patients with ALS from the prospective cohort were enrolled in this study. A multivariable prediction model for the correlation between peak expiratory flow (PEF) and hematologic, biochemical laboratory parameters, and clinical factors in patients with ALS was created. Along with female patients, bulbar-onset, lower body mass index (BMI), later age of onset, lower level of creatinine, uric acid, triglyceride, and a higher level of high-density lipoprotein cholesterol (HDL_C) were related to reduced PEF. The area under the receiver operating characteristics (ROC) curve is.802 for the test set and.775 for the validation set. The study constructed a multivariable prediction model for PEF in patients with ALS. The results can be helpful for clinical practice to predict respiratory impairment.

Glutamatergic synapses from the insular cortex to the basolateral amygdala encode observational pain.

Empathic pain has attracted the interest of a substantial number of researchers studying the social transfer of pain in the sociological, psychological, and neuroscience fields. However, the neural mechanism of empathic pain remains elusive. Here, we establish a long-term observational pain model in mice and find that glutamatergic projection from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for the formation of observational pain. The selective activation or inhibition of the IC-BLA projection pathway strengthens or weakens the intensity of observational pain, respectively. The synaptic molecules are screened, and the upregulated synaptotagmin-2 and RIM3 are identified as key signals in controlling the increased synaptic glutamate transmission from the IC to the BLA. Together, these results reveal the molecular and synaptic mechanisms of a previously unidentified neural pathway that regulates observational pain in mice.

A case report and literature review: subcutaneous panniculitis-like T-cell lymphoma with liver failure as the main manifestation.

Background: Subcutaneous lipofuscinosis-like T-cell lymphoma (SPTCL) is a rare cutaneous lymphoma that often presents as recurrent subcutaneous nodules and may progress to hemophagocytic syndrome with fever and hepatic impairment in some patients. However, no cases of progression to hepatic failure have been reported. Here, we present a case of an adult diagnosed with fever and liver failure as the main manifestation, which was eventually confirmed as SPTCL by skin biopsy, but the patient eventually died due to disease progression. Case Description: This study retrospectively reports a rare case of SPTCL in a 34-year-old female patient who was admitted with scleral jaundice for 1 month and fever for 20 days. Examination revealed multiple small subcutaneous nodules on the skin of the chest and tibial surface and an enlarged liver and spleen. Laboratory tests revealed hepatic impairment, and common causes of liver failure (viral infection, fatty liver, immune liver damage, etc.) were excluded. We continued to refine the positron emission tomography-computed tomography (PET-CT) examination, which revealed multiple flocculent and nodular hyperdense shadows with increased metabolism in the subcutaneous fat interstices. And then, we performed a skin biopsy and the final pathological diagnosis was SPTCL, but the patient died 1 month after diagnosis due to poor treatment outcome because the disease progressed too rapidly. With this case report, we hope to improve clinicians' understanding of liver injury caused by SPTCL. A review of the literature revealed that this is the first case report in the literature of SPTCL leading to severe liver failure. Conclusions: For patients presenting with fever and liver injury, primary liver disease cannot simply be assumed, as this presentation may be a manifestation of some extra-hepatic diseases, including SPTCL. For this condition, early detection and early diagnosis may improve the prognosis of patients.

Research trends of prostatitis over past 20 years: A bibliometric analysis.

In the past two decades, thousands of documents in the field of prostatitis have been published. This bibliometric analysis aimed to assess the characteristics, hotspots and frontiers trend of global scientific output on prostatitis. With the trend of moderate growth, altogether 2,423 papers were reviewed. The leading role of the United States in global prostatitis research was obvious, while China had developed rapidly in recent years. Queen's University and JOURNAL OF UROLOGY were the most prolific affiliation and journal respectively. Nickel, J. C made the greatest contribution to the field of prostatitis. Five hotspots have been confirmed: (a) male infertility associated with prostatitis and the molecular mechanisms; (b) diagnosis and treatment of prostatitis; (c) inflammation, pain and bladder irritation symptoms; (d) relationship between chronic prostatitis/chronic pelvic pain syndrome, benign prostatic hyperplasia and prostate cancer; (e) epidemiology, complications of prostatitis and improvement of acupuncture. This bibliometric analysis reveals that the international cooperation was becoming more and more close. Hotspot analysis shows that the molecular mechanism of prostatitis will be a hotspot in the future, mainly focussing on inflammatory immunity and oxidative stress.

Zihuai recipe alleviates cyclophosphamide-induced diminished ovarian reserve via suppressing PI3K/AKT-mediated apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zihuai recipe (ZHR), a Chinese herbal prescription, is widely used for the clinical treatment of Diminished ovarian reserve (DOR) infertility. However, little is known regarding its underlying mechanisms of DOR treatment. AIM OF THE STUDY: This study aimed to investigate the beneficial effects of ZHR on the treatment of DOR and to reveal the underlying mechanisms. MATERIALS AND METHODS: Sixty female 8-week-old Sprague-Dawley rats were randomly divided into the following six groups (n=10 per group): control, DOR, low-dose(2.7 g/kg/day) ZHR (L-ZHR), medium-dose(5.4 g/kg/day), ZHR (M-ZHR), high-dose(10.8 g/kg/day) ZHR (H-ZHR), and hormone replacement therapy (HRT) treatment groups. The DOR model was established in all the groups, except the control group, by a single intraperitoneal injection of 90 mg/kg cyclophosphamide. After the induction of the DOR model, rats were weighed and administered either the relevant dose of ZHR or an equal volume of saline solution (in the control and DOR groups). Rats in the HRT group received estradiol valerate tablets (0.16 mg/kg/day), and with medroxyprogesterone acetate tablets (0.86 mg/kg/day) added on day 4. After 32 days of treatment, the rats were euthanized and the ovaries were collected for sampling. Ovarian morphology was observed by hematoxylin and eosin staining and the number of follicles was counted under a microscope. The serum levels of anti-Müllerian hormone (AMH), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were quantified by ELISA. A TUNEL assay was used to analyze the level of apoptosis of the ovarian cells. The protein expressions of p-PI3K, p-AKT, PI3K, AKT, cleaved caspase-3, BAX, and Bcl-2 were measured by western blotting and immunohistochemistry. Data analysis was performed with SPSS 20.0 software. RESULTS: ZHR administration increased the ovarian index and the serum levels of AMH, GnRH, and E2, while lowering those of FSH and LH. ZHR treatment also increased the number of primordial, primary, secondary, and antral follicles, as well as the number of corpora lutea, but decreased the number of atretic follicles. Furthermore, ZHR administration decreased the percentage of TUNEL-positive ovarian cells. After treatment with ZHR, the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, cleaved caspase-3 and BAX were decreased, whereas the level of Bcl-2 was increased. CONCLUSIONS: ZHR improved the ovarian reserve in CTX-induced DOR rats. The mechanisms of ZHR on DOR may be mediated through the regulation of gonadal hormones of the hypothalamic-pituitary-ovarian axis (HPOA), and the inhibition of PI3K/AKT-mediated apoptosis in granulosa cells.

Neurotensin Attenuates Nociception by Facilitating Inhibitory Synaptic Transmission in the Mouse Spinal Cord.

Neurotensin (NT) is an endogenous tridecapeptide in the central nervous system. NT-containing neurons and NT receptors are widely distributed in the spinal dorsal horn (SDH), indicating their possible modulatory roles in nociception processing. However, the exact distribution and function of NT, as well as NT receptors (NTRs) expression in the SDH, have not been well documented. Among the four NTR subtypes, NTR2 is predominantly involved in central analgesia according to previous reports. However, the expression and function of NTR2 in the SDH has not yet been directly elucidated. Specifically, it remains unclear how NT-NTR2 interactions contribute to NT-mediated analgesia. In the present study, by using immunofluorescent histochemical staining and immunohistochemical staining with in situ hybridization histochemical staining, we found that dense NT- immunoreactivity (NT-ir) and moderate NTR2-ir neuronal cell bodies and fibers were localized throughout the superficial laminae (laminae I-II) of the SDH at the light microscopic level. In addition, γ-aminobutyric acid (GABA) and NTR2 mRNA were colocalized in some neuronal cell bodies, predominantly in lamina II. Using confocal and electron microscopy, we also observed that NT-ir terminals made both close contacts and asymmetrical synapses with the local GABA-ir neurons. Second, electrophysiological recordings showed that NT facilitated inhibitory synaptic transmission but not glutamatergic excitatory synaptic transmission. Inactivation of NTR2 abolished the NT actions on both GABAergic and glycinergic synaptic release. Moreover, a behavioral study revealed that intrathecal injection of NT attenuated thermal pain, mechanical pain, and formalin induced acute inflammatory pain primarily by activating NTR2. Taken together, the present results provide direct evidence that NT-containing terminals and fibers, as well as NTR2-expressing neurons are widely distributed in the spinal dorsal horn, GABA-containing neurons express NTR2 mainly in lamina II, GABA coexists with NTR2 mainly in lamina II, and NT may directly increase the activity of local inhibitory neurons through NTR2 and induce analgesic effects.

Dissolution and mineralization behaviors of HA coatings.

The dissolution and mineralization behavior of HA coatings are two of the main factors governing the bioactivity of coatings. After different post treatment operators, the plasma-sprayed HA coatings have different characteristics, including different chemical composition, crystallinity, crystallite size and dissolution behavior. In this study, HA coatings were characterized by X-ray diffraction, scanning electron microscope, and Fourier transform infrared spectra before and after immersion in simulated body fluid (SBF). When immersed in SBF, both dissolution and precipitation occurred at the same time, but the kinetics of dissolution was quite different from that of precipitation. The former was dominated by ion exchange, while the latter was controlled by the ion concentration product and the solubility of the particles. Therefore, the dissolution behaviors of phosphate ions partly depended on the dissolution behaviors of calcium ions. With the increase of ions concentration in solution by dissolution, more nucleation sites appeared on the surface of coatings. Crystalline grains gradually grew up on the nucleation sites and developed into biomineral layers. The biomineral layers were the results of the precipitation of the ions in the solution; and the carbonates partially substituted phosphates to form bone-like apatite. The different dissolution characters resulted in quite different morphology of the biomineral layers: the coatings with low solubility induced biomineral layers of large grains; on the contrary, the biomineral layers of network structure were observed on the more soluble coatings.